Gluten sensitive enteropathy (GSE) is a common chronic small bowel disorder of autoimmune origin occurring both in children and adults. It is evoked and maintained by wheat gluten which is also present in other cereals. The clinical appearance of GSE is typically coeliac disease (CD). In some individuals, however, it is associated with dermatitis herpetiformis (DH), a bullous, autoimmune skin disease characterised by granular IgA staining of the papillary dermis. Both of these forms of GSE have the same genetic background and have been associated with HLA class II antigens DQ2, and DR3, and the HLA-A1, -B8, -DR3 haplotype. In case of ingestion of gluten and the presence of genetic predisposition, a T-cell mediated autoimmune response develops in the small bowel first resulting in lymphocytic infiltration, later reduction followed by total atrophy of the villi leading to a disturbed resorption (Marsh M N et al., Bailliere Clin Gastr 1995.9:273-294). On a completely gluten-free diet, however, the pathological alterations entirely disappear and a normal morphology and function is restored.
The diagnosis of GSE is based on the characteristic histological changes (villous atrophy, intraepithelial lymphocytosis, crypt hyperplasia) seen in jejunal biopsies, followed by the regeneration of the mucosa after a gluten-free diet and relapse during subsequent gluten challenge. However, serological tests may be helpful in the diagnosis of GSE as they offer a less invasive and cheaper alternative. These detect IgA antibodies directed against endomysial antigen, reticulin, or gliadin. The IgA-class endomysial antibody (EMA) test is considered to be the serological method of choice, because of its higher sensitivity and specificity when compared to the IgA-class anti-reticulin antibody and the IgA-class anti-gliadin antibody tests. EMA is found in 60-70% of untreated patients with DH and in almost all untreated patients with CD. The EMA test is performed, however, on expensive oesophagus sections from endangered primates, is laborious and time consuming, and subjective in borderline cases.
Tissue transglutaminase (TGc, EC 2.3.2.13) was further identified as the predominant or sole endomysial autoantigen of CD (Dieterich W et al., Nature Medicine 1997, 3(7):797-801). An ELISA test for CD has been produced based upon the commercially available guinea pig TGc. Although the amino acid sequence identity between guinea pig and human TGc's is 82.8%, this test gave high sensitivity and specificity above 90% (Ikura K et al., Biochemistry 1988; 27:2898-905; Gentile Vet al., J Biol Chem 1991; 266:478-83; Dieterich W et al., Gastroenterology 1998; 115:1317-21; Sulkanen S et al, Gastroenterology 1998; 115:1322-8).